Association of the adrenergic alpha 2a receptor - 1291C/G polymorphism with weight change and treatment response to mirtazapine in patients with major depressive disorder

Background: Adrenergic α2a receptors (ADRA2A) are expressed in the central nervous system and peripheral tissues. The primary mechanism of action of mirtazapine is the antagonism of central presynaptic α2 receptors. Mirtazapine is reportedly associated with weight gain. Our objective was to determine whether the ADRA2A - 1291C/G polymorphism is associated with weight gain and treatment response to mirtazapine in patients with major depressive disorder (MDD). Methods: The ADRA2A - 1291C/G polymorphism was analyzed in 314 MDD patients and 162 control subjects. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment. Results: No relationship was observed between the ADRA2A - 1291C/G polymorphism and MDD. No significant difference was found between responder and non-responder groups when comparing the ADRA2A genotype distribution with treatment response to mirtazapine. Repeated measures ANOVA with the last observation carry-forward test indicated that after adjusting for baseline body weight, age, and gender, the subjects with the C/C genotype exhibited a greater mean body weight gain than the subjects with the C/G or G/G genotype after 8 weeks of mirtazapine treatment (p = 0.052). Conclusions: The ADRA2A - 1291C/G polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was weakly associated with weight change after 8 weeks of mirtazapine treatment. Further investigation is required to determine whether other polymorphisms of this gene influence treatment response and weight change in patients receiving mirtazapine.